The islets of Langerhans which are distributed throughout the pancreas comprise 1-2% of the mass of the pancreas and contain the endocrine cells that secrete insulin (beta-cells) and other hormones. The overall goal of the studies outlined in this application is to provide a better understanding of normal physiological changes in islet number, size, shape, distribution and cellular composition associated with aging with the expectation that the results will provide a foundation to further study the processes in response to perturbations such as chronic metabolic diseases. Here we propose to use novel large-scale imaging techniques to describe and quantify changes in human pancreatic islets as a function of age. This application is a collaboration between investigators at the University of Chicago and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and has one specific aim: Specific Aim: Quantitative analysis of changes in human pancreatic islets as a function of age The proposed study will provide a detailed understanding of the effect of aging on human pancreatic islets and the genes and pathways involved. The results form the foundation for future studies of human pancreatic islets under physiological and pathophysiological conditions. The primary data and analyses will be made available to the diabetes community through an online library for follow-up analyses. PUBLIC HEALTH RELEVANCE: The overall goal of this project is to characterize the number, size, shape, distribution and cellular composition of human pancreatic islets as a function of age. The results will provide a better understanding of the normal changes in islets that occur as we age and a foundation for similar studies under other physiological and pathophysiological conditions.